
- Defects early in the pathway produce precursors which are neurotoxic and produce acute porphyrias. They show #autosomalDominant inheritance.
- More common are defects later on in the pathway cause accumulation of porphyrins leading to chronic porphyria; This is known as porphyria cutanea tarda.
[!TIP] Patient (esp. Female) with abdominal pain + neuropsychiatric features -> need to consider acute porphyria.
Clinical features: Abdominal pain, neuropsychiatric features, seizures and fever.
Can be precipitated by anaesthetic drugs and luteal phase of the menstrual cycle.
Anaesthesia for suspected acute abdomen can be catastrophic.
The defective enzyme in acute intermittent porphyria is porphobilinogen deaminase.
The defect is in uroporphyrinogen decarboxylase.
80% of cases are acquired / sporadic; 20% are inherited.
Uroporphyrinogen decarboxylase converts uroporphyrinogen III into coproporphyrinogen III.
Presents with photosensitive blistering rash.
Hypertrichosis and hyperpigmentation may be present.
Liver disease is a common comorbidity:
- Either caused by excessive hepatic porphyrins OR
- liver disease due to hepatitic C / alcohol triggering porphyria.
Triggers for attacks are caused by increased hepatic iron load but also alcohol, smoking, estrogens, hepatitis C or HIV.
Phlebotomy - used to decrease the iron load.
Hydroxycholorquine - increase the excretion of porphyrins.

- Cutaneous T cell lymphoma - usually limited to the skin. Looks like tinea versicolor.
- benign course
Sezary syndrome
- Sezary syndrome is an erythrodermic cutaneous T-cell lymphoma with the leukemic component.
1. Overnight 1mg dexamethasone suppression test
- Primary adrenal insufficiency is also called Addison's disease
- Features: ⬇Na, ⬆K, ⬇pH
- Diagnosis
- Screening: morning cortisol level.
- confirmatory: Short synacthen test. (plasma cortisol is measure before and 30 minutes after administration of IM 250ug of Synacthen)
- Other investigations (not related to Addison's disease):
- 24 hour urinary free cortisol is used to check for cushing's syndrome; not Addison's.
Psoriatic arthritis is associated with HLA-B27.
Imaging
Psoriatic arthritis Vs. Rheumatoid arthritis
Differentiation is clinically important because prognosis and management are different.
| better prognosis |
Somewhat worse |
| Early disease -> NSAIDS |
DMARDs started early |
| Dactylitis, enthesistis, tenosynovitis |
- |
| pattern: asymmetric oligo / symmetric, DIP is specific |
Symmetric polyarthritis of PIP / MCP |
| Sacroiliitis |
- |
| Nail changes |
- |
| - |
proximal hand and foot involvement (?wrist and ankles) |
| Source |
|
Summary of enzymes involved
HMG-CoA reductase: Rate limiting enzyme in cholesterol sythesis : found in the liver and ? other tissues
LCAT : the enzyme synthesized by the liver and attached to HDL which exterifies cholesterol so that it becomes trapped inside HDL. Required for reverse transport of cholesterol.
LPL: lipoprotein lipase: the enzyme found on tissues which removes lipids from VLDL and it's derivatives, increasing their density.
If there is acidosis (pH < 7.2 or HCO3 < 15) or high ketonemia, manage as DKA.
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+ it is **non pruritic**, starts on the abdomen and **spreads *outwards***. (Spares palms and soles)
Trombiculid mite = 'harvest' mite
Endemic typhus serves as the prototype for pathogenesis:
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[!INFO] DCT physiology
- Reabsorbs 5% of the filtered potassium.
- Contains thiazide sensitive Na/Cl co-transporter.
- Also contains TRPV-5 for calcium reabsorption.
Inheritance: #autosomal-Recessive
- Thiazides and Gitelman affect the same transporter (NCCT)
These changes (except the lack of hyponatremia) are very similar to changes caused by chronic thiazide use.
8. Endocrine: reduced testosterone (due to Leydig cell dysfunction) [Source](https://emedicine.medscape.com/article/120858-overview)
- Activated charcoal isn't effective
- Long term, may need liver transplantation.
- Antidotes: Ethanol and fomepizole.
| Dermatologic condition | Associated |
| ---- | ---- |
| Hyperkeratotic and proliferative dermatoses | - |
| [[2022 General Medicine Paper-May#Acanthosis nigricans]] | |
| Florid cutaneous papillomatosis (rapid eruption of warts) | Stomach cancer |
| Sign of Leser-Trelat (rapid appearance of seborrheic keratoses) | Gastrointestinal adenocarcinoma AND many others |
| Tripe palm (velvety thickening of palmar skin) | Gastric or lung cancer |
| Icthyosis | Hodgkin's lymphoma |
| Palmoplantar keratoderma | Associated with SQC of oesophagus = Howel-Evans Xn |
| Bazex Xn: psoriatic like plaques on fingers and toes (acrokeratosis paraneoplastica | SQC of aerodigestive tract |
| Inflammatory dermatoses - erythematous or violaceous skin eruptions | |
| Sweet syndnrome (dermal,non vasculitic neutrophil infiltration with fever + neutrophilia) | Acute myeloid leukemia, lymphoma |
| Dermatomyositis | Ovarian, breast, cervical,uterine + others |
| Erythroderma (usually caused by psoriasis or atopic dermatitis) | Cutaneous T cell lymphoma |
| Erythroderma gyratum repens | Bronchogenic carcinoma |
| Pancreatic panniculitis | Pancreatic cancer |
| paraneoplastic pemphigus (PAMS) | Non-hodgkin lymphoma, CLL |
| Mucous Membrane pemphigoid | Unspecified but associated with malignancy |
| - | |
| Hyperpigmentation | |
| Hyperpigmentation in ectopic ACTH poduction (ectopic cushing's syndrome) | Small cell lung CA |
| ( POMC produced by the tumour is a precursor of ACTH and MSH ) | |
| Generalized dermal melanosis | Extensive metastatic melanoma |
| Skin manifestations of amyloidosis [[2022-November#Amyloidosis]] | plasma cell dyscrasias such as multiple myeloma, and less frequently, Waldenström macroglobulinemia |
- reduce alcohol - specially beer, avoid high fructose foods (like soft drinks)
- Reduce total calorie and cholesterol intake.
- Avoid red meat, spinach.
- First few episodes of gout are managed symptomatically as above. (new guidelines recommend ULT from first episode)
- [[Hormone Physiology#Adrenaline synthesis]]
Interface hepatitis is seen, just like autoimmune hepatitis.
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- Serum sickness like syndrome
- Oral lichen planus
- Papular acrodermatitis
- Which is also called ?Gianotti Crosti syndrome
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- and lincosamide - clindamycin.
Symptoms : N/V, headache,
motor effects: nystagmus, tremor, cerebellar ataxia.
Phenytoin side effects
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- TCAs have been overall surpassed by SSRIs probably because of their toxicity
- Mechanism : Inhibition of presynaptic neurotransmitter reuptake
- Toxic effects:
- Cardiac conduction abnormalities ( conduction defects due to increased refractory period, prolonged repolarization) occur during tricyclic antidepressant (TCA) poisoning because TCAs inhibit the fast sodium channels in the His-Purkinje system and myocardium -> slowing down of conduction; Most suggestive feature: widened QRS, prolongation of PR and QT also possible)
- Metabolic acidosis occurs in severe poisoning. Acidosis augments drug toxicity.
- 
- Hypotension From peripheral alpha 1 blockade as well as cardiac effects
- Antimuscarinic effects - tachycardia, hyperthermia, flushing, dilated pupils
- CNS effects: sedation, but may also include confusion, delirium, or hallucinations
- increases pH (goal 7.5) - favors unionised form of the drug -> less affinity to bind to sodium channels.
- Benzodiazepines for agitation
- Saline for hypotension
- Despite prominent anticholinergic toxicity in some, physostigmine is contraindicated (incr. risk of arrest)
Antipsychotic drugs

***
***
- **Commonest** systemic effects are **VICC** - venom induced consumption coagulapathy (venom has a procoagulant effect) and **AKI** - **but overt bleeding usually doesn't occur**. Therefore,
| Drug | Antidote |
| ---- | ---- |
| Kaneru | |
| | |
| | |
***
Causes of hyperprolactinaemia
#2023GM-NOV/Q30
Pathological causes
- Lactotroph adenoma
- Decreased dopaminergic inhibition
- Other hypothalaic or pituitary disorders
Drugs:
- Antipsychotics : commonest drugs causing hyperprolactinaemia (eg. Haloperidol, risperidone)
- Newer drugs: occurs with amisulpride.
- Does not occur with clozapine.
- SSRI's do NOT cause hyperprolactinaemia.
- Other drugs:
- Metoclopramide (centrally acting dopamine and serotonin angatonist) and domperidone (peripherally acting dopamine antagonist) can cause hyperprolactinaemia .
- Domperidone does not cross the blood brain barrier.
- Methyldopa inhibits dopamine synthesis.